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Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.

ABSTRACT: BACKGROUND:Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity. METHODS:We included patients at or above 18?years with suspected septic shock on admission to the intensive care unit (ICU) during 2014 and 2016 to 2018. Plasma samples were collected from ICU admission and every 4?h for 72?h or until death or ICU discharge and batch analysed for HBP. Mean arterial blood pressure (MAP) and noradrenaline dose (NA dose) were recorded at each sampling time point, and systemic vascular resistance index (SVRI) was recorded when available from non-invasive monitoring. The association between HBP, NA dose, MAP and SVRI was assessed respectively using mixed-effects linear regression models. Procalcitonin (PCT) was used as a comparator. RESULTS:A total of 24 patients were included. The kinetics of plasma HBP was highly variable over time, with occasional >2-fold increases and decreases in between 4-h measurements. Every 100?ng/mL increase in HBP corresponded to a 30% increase in NA dose in a crude model (95% CI 3 to 60%, p = 0.03, nobs = 340), a 1.4-mmHg decrease in MAP in an adjusted model (95% CI - 1 to - 2.3?mmHg, p = 0.04) or a 99 dyne s cm-5 m-2 decrease in SVRI in another adjusted model (95% CI - 36 to - 162, p = 0.002, npat = 13). PCT had a stronger association to NA dose than HBP in a crude model but was not significantly associated to NA dose, MAP or SVRI in any time-adjusted model. CONCLUSIONS:Plasma HBP displayed a highly variable kinetic pattern during septic shock and was significantly associated to cardiovascular organ dysfunction severity over time.

SUBMITTER: Tverring J

PROVIDER: S-EPMC7483682 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.

Tverring Jonas J Nielsen Niklas N Dankiewicz Josef J Linder Adam A Kahn Fredrik F Åkesson Per P

Intensive care medicine experimental 20200910 1

<h4>Background</h4>Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity.<h4>Methods</h4>We included patients at or above 18 years with suspected septi ...[more]

PMID: 32910266

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Project description:BackgroundEarly sepsis diagnosis is crucial for the correct management of burn patients, and it clearly influences outcomes. The systemic inflammatory response triggered by burns mimics sepsis presentation and complicates early sepsis diagnosis. Biomarkers were advocated to aid the diagnosis of early sepsis. Serum procalcitonin (PCT) exhibits fair accuracy and good correlation with sepsis severity, being used in diverse clinical settings. However, few studies have evaluated perioperative changes in PCT levels in burn patients. The present study evaluated PCT kinetics during the first days after burn injury and subsequent surgical interventions to assess PCT utility in distinguishing septic from non-septic inflammatory responses.MethodsThis study was a retrospective observational study of all burn patients admitted to the Coimbra Burns Unit (Portugal) between January 2011 and December 2014 who presented with a total burn surface area ≥ 15% and who underwent subsequent surgery. PCT kinetics were investigated a) during the first five days after burn injury and b) preoperatively during the five days after surgery in three subsets of patients, including those with no preoperative and no postoperative sepsis (NN), no preoperative but postoperative sepsis (NS), and preoperative and postoperative sepsis (SS). A total of 145 patients met the selection criteria and were included in the analysis.ResultsPCT levels in the first five days after burn injury were significantly higher in patients who developed at least one sepsis episode (n = 85) compared with patients who did not develop sepsis (n = 60). PCT values > 1.00 ng/mL were clearly associated with sepsis. Study participants (n = 145) underwent a total of 283 surgical interventions. Their distribution by preoperative/postoperative sepsis status was 142 (50.2%) in NN; 62 (21.9%) in NS; and 79 (27.9%) in SS. PCT values exhibited a parallel course in the three groups that peaked on the second postoperative day and returned to preoperative levels on the third day or later. The lowest PCT values were found in NN, and the highest values were observed in SS; the NS values were intermediate.ConclusionsPCT kinetics coupled with a clinical examination may be helpful for sepsis diagnosis during the first days after burn injury and burn surgery.

Project description:OBJECTIVES:Sepsis care is becoming a more common target for hospital performance measurement, but few studies have evaluated the acceptability of sepsis or septic shock mortality as a potential performance measure. In the absence of a gold standard to identify septic shock in claims data, we assessed agreement and stability of hospital mortality performance under different case definitions. DESIGN:Retrospective cohort study. SETTING:U.S. acute care hospitals. PATIENTS:Hospitalized with septic shock at admission, identified by either implicit diagnosis criteria (charges for antibiotics, cultures, and vasopressors) or by explicit International Classification of Diseases, 9th revision, codes. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We used hierarchical logistic regression models to determine hospital risk-standardized mortality rates and hospital performance outliers. We assessed agreement in hospital mortality rankings when septic shock cases were identified by either explicit International Classification of Diseases, 9th revision, codes or implicit diagnosis criteria. Kappa statistics and intraclass correlation coefficients were used to assess agreement in hospital risk-standardized mortality and hospital outlier status, respectively. Fifty-six thousand six-hundred seventy-three patients in 308 hospitals fulfilled at least one case definition for septic shock, whereas 19,136 (33.8%) met both the explicit International Classification of Diseases, 9th revision, and implicit septic shock definition. Hospitals varied widely in risk-standardized septic shock mortality (interquartile range of implicit diagnosis mortality: 25.4-33.5%; International Classification of Diseases, 9th revision, diagnosis: 30.2-38.0%). The median absolute difference in hospital ranking between septic shock cohorts defined by International Classification of Diseases, 9th revision, versus implicit criteria was 37 places (interquartile range, 16-70), with an intraclass correlation coefficient of 0.72, p value of less than 0.001; agreement between case definitions for identification of outlier hospitals was moderate (kappa, 0.44 [95% CI, 0.30-0.58]). CONCLUSIONS:Risk-standardized septic shock mortality rates varied considerably between hospitals, suggesting that septic shock is an important performance target. However, efforts to profile hospital performance were sensitive to septic shock case definitions, suggesting that septic shock mortality is not currently ready for widespread use as a hospital quality measure.

Project description:In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT?<?0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p?=?0.001) and peak PCT levels (p?<?0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p?=?0.002). No differences were seen in terms of other clinical outcomes.In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.

Project description:BackgroundSerum procalcitonin (PCT) evaluation has been proposed for early diagnosis and accurate staging and to guide decisions regarding patients with sepsis, severe sepsis and septic shock, with possible reduction in mortality.ObjectivesTo assess the effectiveness and safety of serum PCT evaluation for reducing mortality and duration of antimicrobial therapy in adults with sepsis, severe sepsis or septic shock.Search methodsWe searched the Central Register of Controlled Trials (CENTRAL; 2015, Issue 7); MEDLINE (1950 to July 2015); Embase (Ovid SP, 1980 to July 2015); Latin American Caribbean Health Sciences Literature (LILACS via BIREME, 1982 to July 2015); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO host, 1982 to July 2015), and trial registers (ISRCTN registry, ClinicalTrials.gov and CenterWatch, to July 2015). We reran the search in October 2016. We added three studies of interest to a list of 'Studies awaiting classification' and will incorporate these into formal review findings during the review update.Selection criteriaWe included only randomized controlled trials (RCTs) testing PCT-guided decisions in at least one of the comparison arms for adults (≥ 18 years old) with sepsis, severe sepsis or septic shock, according to international definitions and irrespective of the setting.Data collection and analysisTwo review authors extracted study data and assessed the methodological quality of included studies. We conducted meta-analysis with random-effects models for the following primary outcomes: mortality and time spent receiving antimicrobial therapy in hospital and in the intensive care unit (ICU), as well as time spent on mechanical ventilation and change in antimicrobial regimen from a broad to a narrower spectrum.Main resultsWe included 10 trials with 1215 participants. Low-quality evidence showed no significant differences in mortality at longest follow-up (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.01; I2 = 10%; 10 trials; N = 1156), at 28 days (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; four trials; N = 316), at ICU discharge (RR 1.03, 95% CI 0.50 to 2.11; I2 = 49%; three trials; N = 506) and at hospital discharge (RR 0.98, 95% CI 0.75 to 1.27; I2 = 0%; seven trials; N = 805; moderate-quality evidence). However, mean time receiving antimicrobial therapy in the intervention groups was -1.28 days (95% CI to -1.95 to -0.61; I2 = 86%; four trials; N = 313; very low-quality evidence). No primary study has analysed the change in antimicrobial regimen from a broad to a narrower spectrum.Authors' conclusionsUp-to-date evidence of very low to moderate quality, with insufficient sample power per outcome, does not clearly support the use of procalcitonin-guided antimicrobial therapy to minimize mortality, mechanical ventilation, clinical severity, reinfection or duration of antimicrobial therapy of patients with septic conditions.

Dataset Information

Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.

Publications

Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.

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